To study whether the circulating anticoagulant, activated protein C (APC), could be a regulator of thrombin activity in basal physiological conditions, fibrinopeptide A and activated protein C levels were determined in samples from 40 healthy individuals. There was a significant inverse correlation between the fibrinopeptide A and APC levels (Spearman rank correlation R = -0.487; P = 0.0023). Because of well-known mechanisms by which decreasing APC levels could cause increased thrombin formation, we suggest that APC may downregulate thrombin activity in subjects with normal protein C levels. Regulation of thrombin formation in health is likely significant for maintaining vascular patency but its molecular mechanisms are poorly understood. The current data suggest that a single physiological anticoagulant, namely APC, may be a significant regulator of procoagulant thrombin activity.